The issue of polymorphism, different crystal structures of the same chemical entity, remains a significant challenge to the chemical community as a whole. In many areas of materials science, such as pharmaceuticals and semiconductors, being able to control and consistently obtain the desired polymorphic form is important as only one form may display the desired physicochemical properties. Therefore, the ability to reliably crystallize the required polymorphic form of a given compound has become essential. Despite significant resources invested by academia and industry to find solutions for controlling polymorphism, there are two significant areas in which control over polymorphism has not been achieved. They are (1) so called hard to crystallize polymorphs, also referred to as disappearing polymorphs, and (2) polymorphs predicted by computational methods that have never been observed experimentally. In the first case, hard to crystallize polymorphs refers to a scenario in which the original crystal form of a compound can no longer be crystallized once a new and more stable form has been obtained. In the second instance, computational methods predict a polymorphic form that is more stable than any observed in the laboratory. However, they cannot be obtained using conventional polymorph screening techniques.
Accordingly, new methods and systems are needed.